Expression of the Neurotensin/Neuromedin N Gene in the Gut

Abstract

Embryologic development of the gastrointestinal (GI) tract represents an important clinical topic, but one that has been, to date, poorly understood. The human GI tract arises during the fourth week of gestation from gut-derived endoderm contacting splanchnic mesoderm (1). Development of the mammalian intestine continues in a cranial to caudal fashion with eventual lining of the entire small bowel and colon by villi (2–5). By the end of the second trimester the human fetal colon has switched to the adult phenotype with loss of the villous architecture and repression of the small intestinal-like pattern of gene expression (6–9). Not only does the gut undergo this broad differential specialization resulting in the functionally and morphologically distinct small bowel and colon but, in addition, a complicated regional differentiation of gene expression and cell lineage patterns are established and maintained along the entire length of the duodenal-to-ileal axis (5,10–12). Furthermore, with maturation and aging, the gut continues to alter its pattern of gene expression and rate of proliferative activity and, in certain instances, can revert to a fetal phenotype or “dedifferentiated” state as noted by expression of fetal genes in ectopic locations (e.g., colon cancers) (9,13–16). Delineating the factors regulating gut differentiation are crucial to our understanding of not only normal gut development and maturation, but also aberrant gut growth. To achieve these goals, “model” intestinal genes are required to better elucidate the complex cellular mechanisms regulating the region-specific patterns of expression, which lead to differentiation and specialized function. Model intestinal genes should possess a number of characteristics: They should be expressed in the adult small bowel, there should be a characteristic temporal-and spatial-specific pattern of gene expression that coincides with developmental changes in the gut, and re-expression of these small bowel genes should also occur with certain neoplastic states (such as certain colon cancers) suggesting a reversion to a fetal pattern of expression. The author has been interested in analyzing the regulation of the gene encoding the gut hormone neurotensin (NT), which possesses many of the characteristics of a model intestinal gene.KeywordsSmall BowelPC12 CellEnteroendocrine CellMedullary Thyroid Carcinoma CellVillous ArchitectureThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.